Human M-ficolin is a secretory protein that activates the lectin complement pathway
Human M-ficolin is a secretory protein that activates the lectin complement pathway
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DOI：
10.4049/jimmunol.175.5.3150
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发表时间：
2005-09-01
影响因子：
4.4
通讯作者：
Fujita, T
中科院分区：
文献类型：
--
作者：
Liu, Y;Endo, Y;Fujita, T
人类已鉴定出三种类型的ficolin: L-ficolin， M-ficolin和H-ficolin。与甘露糖结合凝集素类似，L-ficolin和H-ficolin是凝集素补体途径中的识别分子。另一种人类ficolin， M-ficolin，是一种非血清ficolin，在白细胞和肺中表达；然而，人们对其生理作用知之甚少。在这项研究中，我们报道了M-ficolin在其蛋白定位和凝集素活性方面的特性。M-ficolin定位于肺中性粒细胞、单核细胞和11型肺泡上皮细胞细胞质的分泌颗粒中。在共免疫沉淀实验中，M-ficolin与甘露糖结合凝集素相关丝氨酸蛋白酶(MASP)-1和MASP-2沉淀，表明M-ficolin与MASP -1和MASP-2形成复合物。在C4沉积实验中M-ficolin-MASP复合物在n-乙酰氨基葡萄糖（GIcNAc）包被的微孔板上激活补体。M-ficolin与几种含有GlcNAc、n -乙酰半乳糖胺和唾液- n -乙酰乳胺的新糖蛋白结合，表明M-ficolin可以识别微生物中常见的碳水化合物残基。的确，M-ficolin通过GIcNAc与金黄色葡萄球菌结合。这些结果表明，M-ficolin与其家族成员一样，作为凝集素补体途径的识别分子，在先天免疫中发挥重要作用。
Three types of ficolins have been identified in humans: L-ficolin, M-ficolin, and H-ficolin. Similar to mannose-binding lectin, L-ficolin and H-ficolin are the recognition molecules in the lectin complement pathway. Another human ficolin, M-ficolin, is a nonserum ficolin that is expressed in leukocytes and lung; however, little is known about its physiologic roles. In this study, we report the characterization of M-ficolin in terms of its protein localization and lectin activity. M-ficolin was localized in secretory granules in the cytoplasm of neutrophils, monocytes, and type 11 alveolar epithelial cells in lung. M-ficolin precipitated with mannose-binding lectin-associated serine proteases (MASP)-1 and MASP-2 in a coimmunoprecipitation assay, indicating that M-ficolin forms complexes with MASP-I and MASP-2. M-ficolin-MASP complexes activated complement on N-acetylglucosamine (GIcNAc)-coated microplates in a C4 deposition assay. M-ficolin bound to several neoglycoproteins bearing GlcNAc, N-acetylgalactosamine, and sialyl-N-acetyllactosamine, suggesting that M-ficolin can recognize the common carbohydrate residues found in microbes. Indeed, M-ficolin bound to Staphylococcus aureus through GIcNAc. These results indicate that M-ficolin, like its family members, functions as a recognition molecule of the lectin complement pathway and plays an important role in innate immunity.